2025-01-18_00000218|ligand|9E5F

Discovery of an Orally Bioavailable KRAS G12D Inhibitor; X-ray diffraction 1.35Å

Protein #1 170 residues (100% resolved)

Raw Sequence ...

GMTEYKLVVVGADGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKHKEK

Canonical Sequence ...

GMTEYKLVVVGADGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKHKEK

Non polymer #2 A1BEJ

InChI=1S/C30H28ClFN6O/c1-36(2)17-12-37(13-17)30-27-29(38(14-34-27)28-16-8-23(28)33-11-16)21-10-22(31)24(25(32)26(21)35-30)20-9-18(39)7-15-5-3-4-6-19(15)20/h3-7,9-10,14,16-17,23,28,33,39H,8,11-13H2,1-2H3/t16-,23-,28+/m1/s1

InChI=1S/C30H28ClFN6O/c1-36(2)17-12-37(13-17)30-27-29(38(14-34-27)28-16-8-23(28)33-11-16)21-10-22(31)24(25(32)26(21)35-30)20-9-18(39)7-15-5-3-4-6-19(15)20/h3-7,9-10,14,16-17,23,28,33,39H,8,11-13H2,1-2H3/t16-,23-,28+/m1/s1

SMILES: CN(C)C1CN(C1)c2c3c(c4cc(c(c(c4n2)F)c5cc(cc6c5cccc6)O)Cl)n(cn3)[C@H]7[C@@H]8C[C@H]7NC8

CN(C)C1CN(C1)c2c3c(c4cc(c(c(c4n2)F)c5cc(cc6c5cccc6)O)Cl)n(cn3)[C@H]7[C@@H]8C[C@H]7NC8

Non polymer #3 GDP

InChI=1S/C10H15N5O11P2/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(25-9)1-24-28(22,23)26-27(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1

SMILES: c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)OP(=O)(O)O)O)O)N=C(NC2=O)N

c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)OP(=O)(O)O)O)O)N=C(NC2=O)N

Non polymer #4 MG

InChI=1S/Mg/q+2

SMILES: [Mg+2]

[Mg+2]

Biounit #1 monomer

Reference